rs12439822

Variant names:

• chr15-22860320-T-C
• rs12439822
• NM_030922.7:c.288-309T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030922.7(NIPA2):​c.288-309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,094 control chromosomes in the GnomAD database, including 16,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (16453 hom., cov: 33)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.85
• Publications: 1 publications found

Genes affected

NIPA2 (HGNC:17044): (NIPA magnesium transporter 2) This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-22860320-T-C is Benign according to our data. Variant chr15-22860320-T-C is described in ClinVar as [Benign]. Clinvar id is 1222352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.288-309T>C		intron_variant	Intron 6 of 7	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.288-309T>C		intron_variant	Intron 6 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66129 AN: 151976 Hom.: 16456 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 66122 AN: 152094 Hom.: 16453 Cov.: 33 AF XY: 0.438 AC XY: 32576 AN XY: 74336

African (AFR) AF: 0.190 AC: 7873 AN: 41498

American (AMR) AF: 0.439 AC: 6710 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1447 AN: 5172

South Asian (SAS) AF: 0.530 AC: 2550 AN: 4812

European-Finnish (FIN) AF: 0.654 AC: 6919 AN: 10586

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37719 AN: 67972

Other (OTH) AF: 0.424 AC: 893 AN: 2104

Alfa AF: 0.463 Hom.: 2275

Bravo AF: 0.412

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.67
PhyloP100		1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12439822; hg19: chr15-23012748;